Process for 4-alkyl-2,6-dinitrochlorobenzenes

ABSTRACT

4-Isopropyl-2,6-dinitrochlorobenzene and 4-tert-butyl-2,6dinitrochlorobenzene are prepared in high yields via chlorination of the corresponding 2,6-dinitro phenols with thionyl chloride in the presence of dimethylformamide and a C6-C10 alkyl hydrocarbon solvent. The 4-alkyl-2,6-dinitrochlorobenzenes obtained thereby are useful intermediates of the herbicidally active dinitroanilines.

U United States Patent 51 3,665,042 Tao May 23, 1972 [54] PROCESS FOR4-ALKYL-2,6- Primary ExaminerLeland A. Sebastian DINITROCI-[LOROBENZENESAttorney-Everet F. Smith and Walter E. Buting [72] Inventor: Eddie V. P.Tao, Indianapolis, Ind. [57] ABSTRACT [73] Assignee: Eli Lilly andCompany lndlanapohs 4-lsopropyl-2,-dinitrochlorobenzene and4-tert-butyl-2,6- [22] Filed: May 22, 1970 dinitrochlorobenzene areprepared in high yields via chlorination of the corresponding2,6-dinitro phenols with thionyl N 39 876 [2l] Appl O chloride in thepresence of dimethylformamide and a C -C alkyl hydrocarbon solvent. The4-alkyl-2,6- [52] U.S. Cl ..260/646, 71/125 dinitmchlorobenzenesobtained thereby are useful intep l Cl "C07c 79/12 mediates of theherbicidally active dinitroanilines, [58] Field of Search ..260/646 3Claims, No Drawings [56] References Cited UNITED STATES PATENTS3,005,031 10/1961 Friedrich ..260/646 PROCESS FOR 4-ALKYL-2,6-DINITROCHLOROBENZENES BACKGROUND OF THE INVENTION4-Alkyl-2,6-dinitrochlorobenzenes are useful intermediates for thepreparation of the herbicidally active, 4-alkyl-2,6- dinitroanilines asdescribed in U. S. Pat. No. 3,257,190. For example, the4-alkyl-2,6-dinitrochlorobenzene is reacted with the desired secondaryalkyl amine in an appropriate solvent to yield the desired aniline.

The 4-alkyl-2,G-dinitrochlorobenzenes are prepared from thecorresponding dinitro phenols by chlorination, the phenolic hydroxylgroup being replaced by the chloro substituent. One presently knownmethod for converting a 4-alkyl-2,6- dinitrophenol to the corresponding4alkyl- 2,6dinitrochlorobenzene comprises the reaction of the phenolwith thionyl chloride in the presence of dimethylformamide as describedin the J. Pharm. Soc. Japan, 85, 544 (1965). Although generally asatisfactory method for preparing 4-nitro and 4-halo substitutedcompounds, the method as presently practiced for the preparation of4-isopropyl- 2,6dinitrochlorobenzene and 4-tert-butyl-2,6-dinitrochlorobenzene affords these products contaminated withsubstantial amounts of unreacted phenol. Consequently the reactionproducts require recrystallization to insure sufficient purity forsubsequent reactions. As presently practiced, the thionyl chloride-DMFchlorination reaction is carried out in solvents such as benzene,toluene, carbon tetrachloride and ethylene dichloride in which thereaction product and unreacted phenol are substantially soluble.Evaporation of the solvent and recrystallization of the reaction productmixture is necessary to obtain the chlorinated products 4-isopropyland4-tert-butyl 2,6-dinitrochlorobenzene in the desired state of purity.From the standpoint of a large scale manufacturing process, theevaporation and recrystallization steps required to isolate these twochemical intermediates are disadvantageous and costly. Consequently,there is a need for an improved method for preparing the 4-isopropyl and4-tertbutyl-2,6-dinitrochlorobenzenes from the corresponding phenolswhich is amenable to a less costly isolation procedure. It is an objectof this invention to provide improved process condi- SUMMARY Accordingto the practice of this invention a 4-alkyl-2,6- dinitrophenolrepresented by the formula wherein R is iso-propyl or tert-butyl, isreacted with thionyl chloride in the presence of dimethylformamide (DMF)and a C to C alkyl hydrocarbon solvent to yield a 4-alkyl-2,6-dinitro-chlorobenzene represented by the formula OgN wherein R has thesame meanings as previously defined. The chlorination reaction iscarried out at a temperature between about 65 C. and C. for about 5 to 7hours. The reaction mixture is cooled to room temperature and a 5percent aqueous solution of sodium bicarbonate is added with stirring.The reaction product which precipitates is filtered and washed withwater and alkyl hydrocarbon solvent to yield the crystalline4-alkyl-2,6-dinitrochlorobenzene essentially uncontaminated withunreacted 4-alkyl-2,6-dinitrophenol.

DETAILED DESCRIPTION The process improvements described herein for themanufacture of 4-isopropyland 4-tert-butyl-2,6- dinitrochlorobenzene viathe thionyl chloride-DMF chlorination of the corresponding2,6-dinitrophenol comprise the use of a C -C alkyl hydrocarbon solvent.

The 4-isopropylor 4-tert-butyl-2,6-dinitrophenol is chlorinated withthionyl chloride in the presence of a catalytic amount of DMF at atemperature between about 65 and 95 C. The chlorination reaction iscarried out in an inert hydrocarbon solvent selected from among the C Calkyl hydrocarbons such as hexane, heptane, octane, isooctane, nonane,decane and the like. The preferred alkyl hydrocarbon solvent of thisinvention is n-hexane.

The ratio of 4-alkyl-2,6-dinitrophenol to alkyl hydrocarbon solventemployed may vary somewhat; however it is preferable to use a ratio ofabout 1 g. of phenol to about 1 ml. or less of alkyl hydrocarbonsolvent. When the above specified ratio is employed the reaction isgenerally completed in about 5 to 7 hours. When more solvent is used,the reaction time increases with increased dilution.

The chlorinating agent, thionyl chloride, is employed in excess withrespect to the dinitrophenol. A molar excess of between about 25 percentto about 45 percent can be employed, the preferred molar excess beingabout 40 percent.

Other chlorinating agents such as phosphorus oxychloride, phosphoruspentachloride and phosgene can be employed in the present process;however, thionyl chloride is the much preferred chlorinating agent. Thephosphorus chlorides present purification problems and phosgene gas hasundesirable toxic properties, whereas the liquid thionyl chloride isconveniently handled and its reaction products, hydrogen chloride andsulfur dioxide, escape from the reaction mixture.

As previously mentioned, the chlorination reaction with thionyl chlorideis carried out in the presence of a catalytic amount of DMF. The termcatalytic amount refers to an amount of DMF corresponding to a ratio ofDMF to 4-alkyl- 2,6-dinitrophenol of between about 10 ml. of DMF permole of dinitrophenol to about 40 ml. of DMF per mole of dinitropheno.The preferred ratio is 20 ml. of DMF per mole of4-alkyl-2,6-dinitrophenol. When amounts of DMF in excess of thecatalytic amount are employed, the solubility of the reaction product, a4-alkyl-2,6-dinitrochlorobenzene in the chlorination reaction mixture isincreased and thereby results in more difficult isolation.

Generally the chlorination reaction is performed by adding the4-isopropylor 4-t-butyl-2,6-dinitrophenol to a reaction vesselcontaining the desired amounts of the alkyl hydrocarbon solvent and DMF.The mixture is heated to the reaction temperature and thionyl chlorideis slowly added by dropwise addition. The reaction mixture is maintainedat the reaction temperature for about 5 to 7 hours and is then allowedto cool slowly to room temperature. Generally, when R in the aboveformula represents tert-butyl, the reaction product4-tertbutyl-2,6-dinitrochlorobenzene precipitates from the reactionmixture above room temperature as the mixture is cooling. When R in theabove formula represents isopropyl, the reaction product,4-isopropyl-2,-dinitrochlorobenzene forms a crystalline precipitate asthe reaction mixture is cooled to a temperature of about 10 C.Frequently, however, the reaction products precipitate as oils from thechlorination mixture on cooling. According to the practice of thisinvention, it is preferable to add to the reaction mixture on cooling anaqueous 5 percent solution of sodium bicarbonate in an amount sufficientto react with any excess thionyl chloride or free hydrogen chloride Thecrystallization of the reaction products is thereby enhanced.

The reaction products of the present improved process, 4isopropyl-2,G-dinitrochlorobenzene or 4-tert-butyl-2,6-dinitrochlorobenzene, thus obtained as crystalline precipitates areessentially free of unreacted 4-alkyl-2,6-dinitrophenol, the predominantcontaminant. The chlorobenzene intermediates provided by the improvedprocess described herein are obtained in yields of greater than 90percent and commonly contain only 1 percent or less of the unreacted4-alkyl-2,6- dinitrophenol as determined by UV. spectrophotometry. Theproducts can be used without further purification in the synthesis ofthe herbicidally active N,N-di-n-propyl-4- isopropyl-2,6dinitroanilineas described in U. S. Pat. No. 3,257,190 andN,N-di-n-propyl-4-t-butyl-2,6-dinitroaniline as described in BritishPat. No. 917,253.

As previously noted, a conventional method for converting a4-alkyl-2,6-dinitrophenol to a 4-alkyl-2,6- dinitrochlorobenzene makesuse of inert reaction solvents such as benzene, toluene, carbontetrachloride, chloroform and ethylene dichloride. Whereas the use ofone of these solvents in the thionyl chloride-DMF chlorination reactionaffords acceptable product yields, the 4-isopropylor 4-t-butyl-2,6-dinitrochlorobenzenes do not precipitate from the reaction mediumand therefore require isolation and purification to achieve satisfactorypurity. By employing the improved process of the present inventioncomprising the use of a C to C alkyl hydrocarbon solvent, and preferablycomprising the use of an n-hexane, the 4-isopropylor 4-t-butyl-2,6-dinitrochlorobenzenes are obtained in excellent purity and yielddirectly from the chlorination reaction mixture.

The following Examples more fully illustrate the improved process of thepresent invention.

EXAMPLE 1 4-Isopropyl-2,o-dinitrochlorobenzene To a suspension of 452 g.(2 moles) of 4isopropyl-2,6 dinitrophenol in 400 ml. of n-hexane wasadded 40 ml. of dimethylformamide. The mixture was heated to atemperature between 4050 C., and 333 g. (2.8 moles) of thionyl chloridewas added dropwise. Following addition of the thionyl chloride thereaction mixture was refluxed for 5 hours and cooled to roomtemperature. To the cooled reaction mixture was added 125 ml. of a 5percent solution of sodium bicarbonate and the reaction was stirred for30 minutes. The crystalline reaction product was filtered and washedwith water and hexane and was air dried to afford 456 g. (93 percentyield) of 4-isopropyl-2,G-dinitrochlorobenzene melting at about 61.5-649 C.

EXAMPLE 2 4-tert-Butyl-2,-dinitrochlorobenzene To a suspension of 24 g.(0.1 mole) of 4-tert-butyl-2,6- dinitrophenol in 20 ml. of hexane wereadded 2 ml. of dimethylformamide and the mixture was warmed to about 50C. To the warm mixture was added dropwise 16.6 g. (0.14 mole) of thionylchloride and following addition the reaction mixture was heated at thereflux temperature for 5 hours. The reaction mixture was then cooled toroom temperature and 7 ml. of a 5 percent solution of sodium bicarbonatewere added with stirring. The crystalline precipitate was filtered andwas washed with water and hexane and air dried to yield 24 g. (93percent yield) of 4-tert-butyl-2,fi-dinitrochlorobenzene, melting atabout 113-ll4.5 C.

lclaim:

' 1. In the process for preparing a 4-alkyl-2,6-dinitrochlorobenzene ofthe formula wherein R is isopropyl or tert-butyl, which comprisesheating a

2. In the improved process of claim 1, the further improvement whichcomprises adding a dilute aqueous solution of sodium bicarbonate to thecooled reaction mixture subsequent to the reaction to enhance thecrystallization of the product.
 3. The improved process of claim 1wherein the alkyl hydrocarbon solvent is n-hexane.